Dose Reduction or Discontinuation of Biological Therapy in Patients with Rheumatoid Arthritis in Remission – 1-Year Results of a Guideline-Directed Longitudinal Cohort Study

Cecilie Heegaard Brahe¹, Simon Krabbe², Mikkel Østergaard³, Henrik Rogind⁴, Hanne Slott Jensen³, Annette Hansen⁵, Jesper Nørregaard⁶, Søren Jacobsen⁷, Lene Terslev⁸, Tuan K. Huynh⁹, Dorte Vendelbo Jensen⁵, Natalia Manilo¹⁰, Karsten Heller Asmussen¹¹, Per Brown-Frandsen⁷, Mikael Boesen¹², Zoreh Rastiemadabadi¹³, Daniel Glinatsi¹⁴, Lone Morsel-Carlsen¹⁵, Jakob M. Møller¹⁶, Niels Steen Krogh¹⁷ and Merete Lund Hetland^3,18, ¹Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Denmark, Glostrup, Denmark, ²Center for Rheumatology and Spine diseases, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Denmark, Glostrup, Denmark, ³Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Denmark, Copenhagen, Denmark, ⁴Center for Rheumatology and Spine Diseases, Center for Rheumatology and Spine Diseases, Rigshospitalet - Glostrup, University of Copenhagen, Denmark, Glostrup, Denmark, ⁵DANBIO, On behalf of Depts of Rheumatology, North, South, Central, Zealand and Capital Region, Copenhagen, Denmark, ⁶Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark, ⁷Center for Rheumatology and Spine Diseases, Rigshospitalet - Glostrup, University of Copenhagen, Denmark, Glostrup, Denmark, ⁸Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Copenhagen Center for Arthritis Research (COPECARE), Copenhagen, Denmark, ⁹Department of Rheumatology, Copenhagen University Hospital at Nordsjælland, Denmark, Hillerød, Denmark, ¹⁰The DANBIO registry and the Danish Departments of Rheumatology, Copenhagen, Denmark, ¹¹Department of Rheumatology, Copenhagen University Hospital at Frederiksberg-Bispebjerg, Denmark, Frederiksberg, Denmark, ¹²Frederiksberg Hospital, Parker Institute, Frederiksberg, Denmark, ¹³Department of Radiology, Frederiksberg Hospital, Frederiksberg, Denmark, ¹⁴Center for Rheumatology and Spine Diseases, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark, Glostrup, Denmark, ¹⁵Department of Radiology, Rigshospitalet, Copenhagen, Denmark, ¹⁶Department of Radiology, Copenhagen University Hospital Herlev and Gentofte, Herlev, Denmark, ¹⁷Zitelab, Frederiksberg, Denmark, ¹⁸Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, The Danish Rheumatologic Database (DANBIO), Glostrup Hospital., Copenhagen, Denmark

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Biologic drugs, outcomes and rheumatoid arthritis (RA)

Session Information

Date: Tuesday, November 15, 2016

Title: Rheumatoid Arthritis – Clinical Aspects IV: Managing Patients in Remission

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Dose tapering in patients in remission has previously proven promising in randomized controlled trials. However, systematic implementation in clinical practice is lacking. A new guideline in the Capital Region of Denmark required that RA patients in sustained remission on biological therapy must attempt dose reduction according to a predefined algorithm. We aimed to 1) report the 1-year results of the implementation of the guideline and 2) investigate potential clinical baseline predictors of flare during the 1^st year.

Methods: Patients with disease activity score (DAS28, 4 variables, CRP-based) ≤2.6 for ≥1 year and no radiographic progression the previous year were included. According to the algorithm, dosing of biological drug was to be reduced to 2/3 of standard dose at baseline, to ½ of standard dose after 4 months, and discontinued after 8 months. Patients who flared stopped tapering and were escalated to the previous dose to regain remission. Flare was defined as 1) DAS28≥2.6 AND DDAS28≥1.2 since baseline, or 2) erosive progression based on X-ray and/or magnetic resonance imaging (MRI). The relapse-free time since start of tapering stratified by gender and by median disease duration (11 years) was presented as Kaplan-Meier curves (time to flare). Breslow test was applied to test for significant difference between men and women and disease duration.

Results: A total of 143 patients from 5 departments of rheumatology were included as part of the implementation of the guideline. Baseline characteristics and medication are shown in table 1. During the 1st year, 101 (71%) patients flared and stopped tapering. All patients who flared were re-escalated and regained remission. At 1 year, 49 (34%) were on full dose, 28 (20%) patients were on 2/3 dose, 36 (25%) on half dose, and 30 (21%) had discontinued biological treatment. Median time to flare was 273 days (IQR: 247-299). According to figure 1 female sex and longer disease duration were associated with an increased risk of flare.

Conclusion: One year after initiating dose tapering in RA patients in remission in routine clinical practice, 66% of patients had been able to reduce the dose. Flares during tapering occurred in >70%, but were reversed by re-escalating patients to the previous dose. Female sex and longer disease duration were associated with increased risk of flare.

Disclosure: C. H. Brahe, None; S. Krabbe, None; M. Østergaard, Abbott Immunology Pharmaceuticals, 2,Bristol-Myers Squibb, 2,Boehringer Ingelheim, 2,Eli Lilly and Company, 2,Merck Pharmaceuticals, 2,Pfizer Inc, 2,Roche Pharmaceuticals, 2,UCB, 2,Celgene, 2,Sanofi-Aventis Pharmaceutical, 2,Regeneron, 2,Novartis Pharmaceutical Corporation, 2; H. Rogind, None; H. S. Jensen, None; A. Hansen, None; J. Nørregaard, None; S. Jacobsen, None; L. Terslev, None; T. K. Huynh, None; D. V. Jensen, None; N. Manilo, None; K. H. Asmussen, None; P. Brown-Frandsen, None; M. Boesen, None; Z. Rastiemadabadi, None; D. Glinatsi, None; L. Morsel-Carlsen, None; J. M. Møller, None; N. S. Krogh, None; M. Lund Hetland, AbbVie, BMS, MSD, Roche, Pfizer, UCB, Crescendo, 2.

To cite this abstract in AMA style:

Brahe CH, Krabbe S, Østergaard M, Rogind H, Jensen HS, Hansen A, Nørregaard J, Jacobsen S, Terslev L, Huynh TK, Jensen DV, Manilo N, Asmussen KH, Brown-Frandsen P, Boesen M, Rastiemadabadi Z, Glinatsi D, Morsel-Carlsen L, Møller JM, Krogh NS, Lund Hetland M. Dose Reduction or Discontinuation of Biological Therapy in Patients with Rheumatoid Arthritis in Remission – 1-Year Results of a Guideline-Directed Longitudinal Cohort Study [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/dose-reduction-or-discontinuation-of-biological-therapy-in-patients-with-rheumatoid-arthritis-in-remission-1-year-results-of-a-guideline-directed-longitudinal-cohort-study/. Accessed .

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